tbuckley/cabot-search huggingface dataset:
Clinical outcomes and healthcare resource utilization (HCRU) in patients (pts) with lower-risk myelodysplastic syndromes (LR-MDS) reinitiating erythropoiesis-stimulating agents (ESAs) following previous ESA treatment.
Authors: Guillermo Garcia-Manero, Rayna K. Matsuno, Ali McBride, Thomas D. Brown, Danny Idryo, Ronda Broome, Autumn Herriman, Tiffany Johnson, Kristiana Wilkinson, Sheetal Walters, Andrew Schrag, Colden Johanson, Monika A. Izano, Sudipto Mukherjee
Journal: Journal of Clinical Oncology (2022)

e19067 Background: The median survival for pts with LR-MDS is estimated to be 5–10 years. ESAs are utilized as first-line treatment for anemia in LR-MDS; however, real-world treatment patterns, clinical outcomes, and HCRU for pts with LR-MDS who reinitiated ESAs following previous discontinuation are not well-established. Methods: This was a retrospective study of pts with LR-MDS in a network of US community health systems who initiated ESAs as first-line therapy between January 1, 2016 and June 30, 2019 and were followed through June 30, 2021. Pts were required to have discontinued (had a ≥ 3-week gap between treatment with epoetin alfa, or a ≥ 6-week gap between treatment with darbepoetin alfa) and subsequently reinitiated ESA therapy at least once during follow-up. Outcomes included failure to achieve transfusion independence (TI), progression to acute myeloid leukemia (AML), overall survival (OS), number and type of health system visits, and medication use. TI was defined per IWG 2006 criteria in the subset of pts who had received ≥ 1 transfusion in the 8 weeks prior to ESA initiation. Results: There were 108 pts with confirmed LR-MDS who initiated ESA-based therapy. Pts had a median age of 79 years at diagnosis (interquartile range [IQR] 73–85), were predominantly male (58%), White (97%), and overweight or obese (52%). The median follow-up period was 17.0 months (IQR 7.2–34.7). The most used ESA was darbepoetin alfa (60%), followed by epoetin alfa (38%) and epoetin alfa-epbx (2%). Of the 33 pts who received a baseline transfusion, 52% did not achieve TI; 53% and 43% failed to achieve TI at 6 and 12 months, respectively. The majority of pts were repeatedly treated with ESAs (n = 61, 56%). Among these patients, 2% progressed to AML and 48% died during follow-up; median OS was 45 months. The median number of health system visits per patient-month was 3.2 (IQR 0.6–4.9); 89%, 62%, and 72% of pts had ≥ 1 outpatient, emergency department, or inpatient visit respectively, with median length of hospitalization of 12 days (IQR 4.8–27.8). Most pts (54%) received an antibiotic at least once during follow-up; overall, use of immunosuppressive therapy (2%) or iron chelation (3%) was rare. Conclusions: In this real-world study of community practice in the USA, reinitiation of ESA treatment after prior discontinuation in LR-MDS was prevalent. In these pts, poor clinical outcomes and frequent health system visits were observed. This study highlights the need to consider alternative treatment options for pts with LR-MDS.
Evaluating survival following severe immune-related adverse events requiring hospitalization.
Authors: Francis Wright, Daniel Myung Kim, Jordyn Silverstein, Michelle Wang, Kimberly de Dios, Arabella Young, Zoe E. Quandt, Sam Brondfield
Journal: Journal of Clinical Oncology (2022)

2666 Background: As immune checkpoint inhibitors (CPI) are increasingly approved for the treatment of multiple cancer types, hospitalizations related to severe immune-related adverse events (irAE) will increase in tandem. Here, we identify patients hospitalized due to irAEs and describe survival outcomes across irAE, CPI, and cancer type. Methods: We identified patients exposed to CPIs who were hospitalized from 1/2012 to 12/2020 at our tertiary care hospital by computationally extracting data from the electronic health record. We then performed manual chart review to include only confirmed irAE-related hospitalizations. Survival outcomes were analyzed using Kaplan-Meyer survival curves with log-rank tests. Results: Of 3137 patients treated with CPIs, 117 were hospitalized for irAEs (cumulative incidence 4%). Of these, 36% had melanoma, 15% had lung cancer, 9% had renal cell carcinoma (RCC), and the rest were distributed across other cancers. The average number of irAE-related hospitalizations per patient was 1.25 (ranging from 1-3). Among 153 irAEs requiring hospitalization, 39% were gastrointestinal (GI) (including hepatitis), 12% endocrine, 12% pulmonary, 12% neurologic, 12% musculoskeletal, 7% cardiovascular, 6% dermatologic, and the rest affected other organs. Across all patients hospitalized for irAEs, median survival following hospitalization was 980 days. Patients with GI and endocrine irAEs had longer median survival (1474 days and median not reached [NR], respectively), while patients with pulmonary irAEs had shorter median survival (64 days) [p=0.002]. Patients with melanoma and RCC had longer median survival (2796 days and NR, respectively), while patients with lung cancer had shorter median survival (165 days) [p=&lt;0.001]. Survival was not significantly different across CPI type [p=0.20]. Conclusions: Although hospitalization for severe irAE was rare, these findings suggest that among these patients, survival differs by irAE and cancer type. This real world data can contribute to clinical models that predict the risk of hospitalization and the risk of death due to severe irAEs, which may inform patient counseling and treatment decision-making. [Table: see text]
Performance of an artificial intelligence-based annotation algorithm for reporting cancer genomic profiling tests.
Authors: Hidenori Kage, Takashi Aoki, Aya Shinozaki-Ushiku, Kousuke Watanabe, Nana Akiyama, Hideaki Isago, Kazunaga Ishigaki, Nariaki Odawara, Yusuke Sato, Kazuhito Sasaki, Shota Tanaka, Michihiro Tanikawa, Motohiro Kato, Masahiko Tanabe, Kenji Tatsuno, Tetsuo Ushiku, Kiyoshi Miyagawa, Kunihiro Nishimura, Hiroyuki Aburatani, Katsutoshi Oda
Journal: Journal of Clinical Oncology (2022)

1551 Background: Cancer genomic profiling (CGP) tests have been approved in Japan since June 2019, with the requisite that all test results be discussed by molecular tumor boards (MTBs). More than 20,000 patients in over 200 designated hospitals have taken CGP tests by December 2021. As CGP tests have entered clinical practice, streamlining decision making by MTBs and standardizing interpretation of test results and treatment recommendations have become urgent issues. Here, we evaluated the utility of Chrovis, an annotation algorithm for reporting CGP tests to support MTBs make their recommendations. Methods: We retrospectively reviewed the reporting process of all approved CGP tests done at The University of Tokyo Hospital between December 2019 and November 2021. Chrovis provided annotation for each genetic variant by incorporating biologic, clinical, and therapeutic information by referencing several public knowledge databases and using natural language processing, and generated reports using the automated program. The MTB reviewed and made any necessary changes before finalizing the report. Changes in disclosure of germline findings were made according to the recommendations of a national guideline with consideration of past and family history. Results: Of the 243 tests, 91 changes in 81 Chrovis reports (33% of all reports) were made by the MTB. The most common type of change was germline disclosure with 26 changes (29%), followed by clinical trial information in Japan (18 changes, 20%) and recommendation of the patient-proposed national basket trial with multiple targeted agents (17 changes, 19%). Changes in germline disclosure increased from June 2021, when an update to a national guideline was released, while the proportion of changes in the latter two types remained unchanged. Gene alterations that led to the highest number of changes was TP53, with 13 changes. Changes in therapeutic recommendations were frequently observed in the RAS/MAPK pathway ( BRAF, KRAS, NF1, NRAS) with 12 changes. More changes were required with a tumor-only tissue CGP panel (57 of 149) compared with a matched tumor/normal tissue CGP panel (24 of 94, p = 0.04), mostly due to germline disclosure (24 vs. 2 changes). Conclusions: We observed that automated algorithm-based reporting was sufficient in 67% of reports. Recommendation for germline disclosure still requires manual supervision, particularly with tumor-only tissue CGP panels if algorithms do not incorporate medical history. The process of recommending clinical trials needs improvement, e.g., standardizing database formats for inclusion and exclusion criteria.
Higher obesity and lower screening rates in Hispanic women and associated increased breast cancer in the United States.
Authors: Michelle Ann P. Caesar, Cheng-I Liao, Danny Lee, Ava Chan, Daniel Stuart Kapp, John K Chan
Journal: Journal of Clinical Oncology (2022)

10555 Background: To evaluate trends in postmenopausal breast cancer and mammogram utilization in Hispanic and White women in the United States. Methods: Data on postmenopausal breast cancer was obtained from the United States Cancer Statistics Public Use Database between 2001 and 2018. Rates of mammogram screening for women ages 18 and older were evaluated using the Behavioral Risk Factor Surveillance System (BRFSS) from 2000 and 2018. Obesity rates for women ages 18 and older were extracted from BRFSS between 2001 and 2016. SEER*Stat 8.3.8 and Joinpoint regression program 4.8.0.1 were used to calculate incidence trends. Breast cancer and obesity incidence and trends were described using average annual percent change (AAPC). Mammogram screening trends were described using average biennial percent change (ABPC). Age groups were divided into five-year or ten-year intervals. Results: Over the past eighteen years, early-stage breast cancer in Hispanic women has increased annually by 1.06% (p = 0.000) and advanced-stage has also increased annually by 0.81% (p = 0.000). In contrast, there was no increase in early-stage cancer in White women, however, advanced stage increased by 1.06% annually (p = 0.000). Compared to White woomen, Hispanic women are more likely to be unscreened with mammograms (18.17% vs. 40.06%). Over time, the unscreened population is decreasing at 3.43% for White women compared to only 1.24% in Hispanic women (p = 0.000, p = 0.001). Overall in the U.S., the never-screened population has decreased biennially by 2.88% (p = 0.000). In 2016, 33.16% of Hispanic women and 28.13% of White women were considered obese, and this obesity rate has been increasing at 2.6% and 2.4%, respectively (p = 0.000). Conclusions: Our data showed that early- and advanced-stage breast cancer has been increasing in Hispanic women in the United States. Hispanic women were also more likely to be obese and less likely to undergo screening compared to White women.
Structural variants shape the genomic landscape and clinical outcome of multiple myeloma
Authors: Cody Ashby, Eileen M. Boyle, Michael A. Bauer, Aneta Mikulasova, Christopher P. Wardell, Louis Williams, Ariel Siegel, Patrick Blaney, Marc Braunstein, David Kaminetsky, Jonathan Keats, Francesco Maura, Ola Landgren, Brian A. Walker, Faith E. Davies, Gareth J. Morgan
Journal: Blood Cancer Journal (2022)

Deciphering genomic architecture is key to identifying novel disease drivers and understanding the mechanisms underlying myeloma initiation and progression. In this work, using the CoMMpass dataset, we show that structural variants (SV) occur in a nonrandom fashion throughout the genome with an increased frequency in the t(4;14), RB1, or TP53 mutated cases and reduced frequency in t(11;14) cases. By mapping sites of chromosomal rearrangements to topologically associated domains and identifying significantly upregulated genes by RNAseq we identify both predicted and novel putative driver genes. These data highlight the heterogeneity of transcriptional dysregulation occurring as a consequence of both the canonical and novel structural variants. Further, it shows that the complex rearrangements chromoplexy, chromothripsis and templated insertions are common in MM with each variant having its own distinct frequency and impact on clinical outcome. Chromothripsis is associated with a significant independent negative impact on clinical outcome in newly diagnosed cases consistent with its use alongside other clinical and genetic risk factors to identify prognosis.
QOL-05. Cardiorespiratory fitness and health-related quality of life amongst survivors of childhood central nervous system tumours.
Authors: Rachael Keating, Sarah Curry, Juliette Hussey
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION: Due to recent advancements in surgical techniques, imaging and adjuvant therapies, survival rates for children with central nervous system (CNS) tumours have improved. Research priorities have now shifted to focus on late-effects and quality of survivorship amongst childhood CNS tumour survivors. Our study aimed to assess levels of cardiorespiratory fitness and health-related quality of life (HRQoL) amongst survivors of childhood CNS tumours. A secondary aim was to investigate potential relationships between cardiorespiratory fitness and HRQoL. METHODS: Participants were recruited from the National Children’s Cancer Service in CHI Crumlin. Inclusion criteria included: diagnosis of a primary CNS tumour, aged between 6-17 years, between 3 months and 5 years post completion of oncology treatment, independent mobility, deemed clinically appropriate to participate by treating oncologist. Cardiorespiratory fitness was assessed using the six-minute walk test. HRQoL was assessed with the PedsQL Generic Core Scales, Version 4.0, both self-report and parent proxy report forms were used. RESULTS: 20 participants (n=9 male) were recruited with a mean age of 12.34 (SD = 3.46) years. Mean time since completion of oncology treatment was 2.31 (SD = 1.38) years. Mean 6-minute walk distance (6MWD) was 482.75 (SD = 50.04) metres, equating to the 5.55th (SD = 6.83th) percentile overall. 6MWD was significantly reduced compared to predicted 6MWD (t = -12.52, p &amp;lt;.001, 95% CI [-163.52, -116.68]). Parent proxy-reported HRQoL was significantly reduced compared to healthy population norms (t = -5.82, p &amp;lt;0.001, 95% CI [-25.76, -12.17]). A strong positive correlation exists between 6MWD and both parent-proxy (Pearson’s r = 0.533, p = 0.015) and child-reported HRQoL (r = 0.580, p = 0.007). CONCLUSION: Survivors of childhood CNS tumours present with impaired levels of cardiorespiratory fitness and HRQoL compared to healthy population norms. Higher levels of cardiorespiratory fitness are associated with higher levels of HRQoL.
Australasian Gastrointestinal Trials Group (AGITG) CONTROL NET Study: <sup>177</sup>Lu-DOTATATE peptide receptor radionuclide therapy (PRRT) and capecitabine plus temozolomide (CAPTEM) for pancreas and midgut neuroendocrine tumours (pNETS, mNETS)—Final results.
Authors: Nick Pavlakis, David Turner Ransom, David Wyld, Katrin Marie Sjoquist, Kate Wilson, Val Gebski, James Murray, Andrew Ddembe Kiberu, Matthew E. Burge, William Macdonald, Paul Roach, David A. Pattison, Patrick Butler, Timothy Jay Price, Michael Michael, Benjamin James Lawrence, Dale L. Bailey, Simone Leyden, John Raymond Zalcberg, Harvey Turner
Journal: Journal of Clinical Oncology (2022)

4122 Background: CAPTEM is an accepted regimen for patients (pts) with advanced pNETs. Single agent PRRT is now a standard of care for progressive WHO Grade 1/2 mNETs. High activity was seen with PRRT/CAPTEM in a single arm Phase I/II trial. This study aims to determine the activity of combining CAPTEM with PRRT in mNETs and pNETs pts. Methods: Non-comparative randomised open label parallel group phase II trial with 2:1 randomisation to PRRT/CAPTEM (experimental arm) vs. PRRT (mNETs control) and CAPTEM (pNETS control). PRRT/CAPTEM: 7.8GBq 177 Lu Octreotate (Lutate) given intravenously (IV) on day 10 every 8 weeks for 4 cycles, with concurrent oral capecitabine 750mg/m 2 b.i.d. days 1-14 and temozolomide 75mg/m 2 b.i.d. days 10-14 every 56 day cycle, up to 4 cycles. PRRT alone: 7.8GBq 177 Lu Octreotate (Lutate) given intravenously (IV) on day 1 every 8 weeks for 4 cycles. CAPTEM alone: Oral capecitabine 750mg/m 2 b.i.d. days 1-14 and days 29-42; Oral temozolomide 75mg/m 2 b.i.d. days 10-14 and 38-42 every 56 day (8w) cycle. Primary endpoint: Progression free survival (PFS). mNETS: At 15 months, assuming PFS 66.4% in control arm; target PFS ³ 80%; pNETS: At 12 months, assuming PFS 60% in control arm; target PFS ³ 75%. Secondary endpoints: Objective tumor response rate (complete or partial) (OTRR), overall survival (OS), adverse events (AEs). Results: 75 pts enrolled (Dec 2015 – Nov 2018): mNETs 33 PRRT/CAPTEM, 14 PRRT, median follow up (mFU) 60.3 months; pNETS 19 PRRT/CAPTEM, 9 CAPTEM, mFU 57.5 months (mo). Late Grade 3/4 haematologic AEs: mNETS: 2/32 (6%) PRRT/CAPTEM pts and 4/13 (31%) PRRT pts. Events included myelodysplastic syndrome (40 mo), leukaemia (60 mo), pancytopenia (50 mo), anaemia (32 mo), thrombocytopenia (7 mo). No late haematologic G3/4 AEs were reported in the pNETS cohort. No late renal toxicity was identified in all study arms. Conclusions: CONTROL NETs is the first randomized trial to demonstrate efficacy for PRRT in pNETs, in addition to a standard of care. Extended follow up confirms durable CAPTEM/PRRT activity, with superior PFS in pNETs. Late haematologic toxicity was seen in both mNET PRRT arms but was not higher with additional CAPTEM. The activity of CAPTEM/PRRT in pNETs should be tested in the phase III setting. Clinical trial information: ACTRN12615000909527. [Table: see text]
Eribulin mesylate versus eribulin plus anlotinib in patients with advanced or metastatic breast cancer: Results of a phase II study.
Authors: Liping Liu, Zhe-Yu Hu, Ning Xie, Xiaohong Yang, Huawu Xiao, Jing Li, Can Tian, Hui Wu, Jun Lu, Jianxiang Gao, Xuming Hu, Min Cao, Zhengrong Shui, Bingliang Liu, Quchang Ouyang
Journal: Journal of Clinical Oncology (2022)

1094 Background: Eribulin mesylate is a structurally simplified, synthetic, macrocyclic ketone analogue of Halichondrin B. We investigated the efficacy and safety of eribulin monotherapy versus eribulin plus the oral anti-angiogenesis inhibitor anlotinib in patients with advanced or metastatic breast cancer. Methods: This Phase II study included adult Chinese patients with locally advanced or metastatic breast cancer previously treated with at least two chemotherapy regimens, including both anthracycline- and taxane-based therapy (NCT05206656). Patients were randomized (1:1) to receive eribulin (1.4 mg/m 2 , intravenously, on days 1−8), alone or in combination with anlotinib (12 mg orally once daily), in 21-day cycles. The primary endpoint was investigator-assessed disease control rate (DCR), per RECIST version 1.1. Key secondary endpoints included objective response rate (ORR), progression-free survival (PFS) and safety. Results: Between February 12, 2020, and July 22, 2021, 56 patients were randomized to eribulin (n=32) or eribulin plus anlotinib (n=24) (Table). Sites of metastasis were: bone (60.7%), lung (52.7%), liver (53.6%), lymph nodes (73.2%) and soft tissue (7.1%). Among all patients, the DCR was 66.7% versus 100% (treatment difference, 33.3%; P=0.007), the ORR was 37.0% versus 38.9%, and the median PFS was 3.7 months versus 9.7 months (adjusted hazard ratio, 0.20; 95% CI, 0.04 to 0.91; P=0.04) for patients receiving eribulin versus eribulin plus anlotinib, respectively. Among 36 (64.3%) patients with triple-negative breast cancer, the DCR was 55.6% versus 72.2% (treatment difference, 16.7%; P=0.300) and the median PFS was 3.6 months versus 9.7 months (log rank P=0.030) with eribulin alone versus eribulin plus anlotinib, respectively. The most frequent grade 3-4 adverse events in the eribulin and eribulin plus anlotinib groups were decreased neutrophil count (25.0% [n=8] vs. 29.2% [n=7]) elevated transaminase (6.3% [n=2] vs. 0.0%) and decreased thrombocyte count (3.1% [n=1] vs. 0.0%), respectively. Conclusions: Eribulin plus anlotinib was associated with a significantly better DCR, ORR and PFS than eribulin monotherapy in patients with locally advanced or metastatic breast cancer previously treated with anthracyclines and taxanes. Clinical trial information: NCT05206656. [Table: see text]
Mutational profile, clinical characterization, and outcomes of lung cancer in solid organ transplant recipients.
Authors: Shenduo Li, Rami Manochakian, Yujie Zhao, Yanyan Lou
Journal: Journal of Clinical Oncology (2022)

e21131 Background: Solid organ transplant recipients have increased risk for malignancies. Lung cancer is the second most common malignancy in this population. Those patients are usually on long-term immunosuppressive medications that may affect tumorigenesis, cancer characteristics, and treatment response. Previous studies have investigated the characteristics and outcomes of post-transplant patients with lung cancer in small-sized cohorts. However, the tumor mutational profile and detailed treatment response at different stages have not been reported. Methods: We conducted a retrospective study from a cohort of 52 solid organ transplant recipients who were diagnosed with lung cancer at Mayo Clinic from 2018 to 2021. We examined tumor molecular alteration using next generation sequencing (NGS), analyzed the treatment modalities, progression-free survival (PFS), and overall survival (OS) and compared those to the general population with lung cancer using historical data in previous large trials. Results: In our study, most transplanted solid organs are kidney (N = 28, 53.8%), followed by liver (N = 12, 23.1%) and heart (N = 9, 17.3%). The adenocarcinoma (N = 28, 53.8%) represented the most common histology, followed by squamous cell carcinoma (N = 19, 36.5%). It consisted of Stage I (30.8%), stage II (15.4%), stage III (25%), and stage IV (26.9%). The most common site of metastasis is bone (64.3%). Transplant recipients with lung cancer have a significantly high frequency of somatic BRCA 1/2 mutations (30.4%), compared to the general population with advanced lung cancer (2.1%, p &lt; 0.001). The frequencies of TP53 mutations (52.2%) and EGFR mutations (30.4%) are also increased. For stage I patients who received surgery or radiation therapy, the disease-free survival (DFS) is 16.5 months. 9 of 14 stage IV patients received chemotherapy. The median number of cycles received is 4. The median PFS is 4.9 months, and the median OS of all stage IV patients is 6.1 months. 4 patients were found to have actionable EGFR mutations, and 3 of them were initially diagnosed with stage IIIA and received Osimertinib after progression. One stage IV patient who was post-liver transplant received pembrolizumab for up to 5 cycles before he developed aspiration pneumonia and then pursued hospice. The PFS is 3.7 months. No immune-related adverse event was reported. Conclusions: In our cohort of solid organ transplant recipients who developed lung cancer, we observed a much higher frequency of somatic BRCA 1/2 mutations, compared to the general population with lung cancer. In addition, our data suggested post-transplant patients with stage I lung cancer have a shorter disease-free survival, and patients with stage IV lung cancer have a shorter overall survival, compared to the general population with lung cancer. Further study containing a high number of solid transplant patients to validate these findings is warranted.